DISP1 Membrane Protein Introduction

Introduction of DISP1

DISP1 is encoded by the DISP1 gene and is also known as Protein dispatched homolog 1 and DISPA. The DISP1 gene is one of two human homologs of Drosophila dispatched, and the encoded protein may play an essential role in hedgehog (HH) patterning activities in the early embryo. DISP1 is a twelve transmembrane domain protein that is required for long-range sonic hedgehog (Shh) signaling. Inhibition of DISP1 function, both by RNAi or dominant-negative constructs, prevents secretion and results in the accumulation of Shh in source cells.

Function of DISP1 Membrane Protein

The action of DISP1 is required in the Shh signaling pathway. DISP1 shares many characteristics with members of the resistance-nodulation-cell division (RND) family of proton-driven transporters. Not only are the overall structures of Disp1 similar to that of bacterial RND permeases, but aspartic acid residues in the fourth transmembrane span, which are thought to be important for proton translocation, are also conserved. It has previously been shown that bacterial RND permeases function as trimers. Similarly, it has been shown that DISP1 is also assembled into trimers. Similar lysates analyzed on an SDS PAGE gel resolves that DISP1 is located basolaterally in polarized epithelial cells and assembles as trimers. DISP1 is required for the basolateral secretion of Shh and lipid-modified. Meanwhile, Shh secretes in a DISP1-dependent manner and is retained in the extracellular matrix.

Fig.1 The signaling pathway of DISP1 in transporting Shh (Boise, 2014).

Application of DISP1 Membrane Protein in Literature

1. Etheridge L.A., et al. Evidence for a role of vertebrate Disp1 in long-range Shh signaling. Development (Cambridge, England). 2010, 137(1):133-140. PubMed ID: 20023168
   
   

   The observations in this article support a dual role for DISP1, not only in the secretion of Shh from the source cells but also in the subsequent transport of Shh through tissue.

2. Jun K.R., et al. Clinical characterization of DISP1 haploinsufficiency: A case report. European Journal of Medical Genetics. 2013, 56(6):309-313. PubMed ID: 23542665
   
   

   This article reveals that deletion or variants of DISP1 have been proposed as a candidate for the midline defects in this syndrome but may not be responsible for its major features in some cases. Meanwhile, the results of this article may help define the role of the DISP1 haploinsufficiency in phenotype and support the suggestion that DISP1 mutation or deletion may reveal incomplete penetrance.

3. Tsiairis C.D., et al. Disp1 regulates growth of mammalian long bones through the control of Ihh distribution. Dev. Biol. 2008, 317(2):480-485. PubMed ID: 18395198
   
   

   The analyses of this article about the Disp1C829F mutation demonstrate that DISP1 is not absolutely required for the paracrine signaling role of Ihh in the skeleton and Disp1 is critical for the full extent of signaling within the chondrocyte target field and consequently the establishment of a normal skeletal growth plate.

4. Roessler E., et al. Truncating loss-of-function mutations of DISP1 contribute to holoprosencephaly-like microform features in humans. Hum. Genet. 2009, 125(4):393-400. PubMed ID: 19184110
   
   

   Authors in this article perform an extensive mutational analysis of the entire human DISP1 gene, required for secretion of all hedgehog ligand and the data of this article suggest that DISP1 function contributes substantially to both of these signs in humans.

5. Lisoway A.J., et al. Pharmacogenetic evaluation of a DISP1 gene variant in antidepressant treatment of obsessive-compulsive disorder. Hum. Psychopharmacol. Clin. Exp. 2018, 33(4):e2659. PubMed ID: 29953682
   
   

   The article investigates the relationship between the DISP1 rs17162912 genotype distribution and serotonin reuptake inhibitor response and there is no observe a significant association between rs17162912 and serotonin reuptake inhibitor response.

DISP1 Preparation Options

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Reference

1. Boise L H. (2014) To Gli or not to Gli. Blood. 124(13):2008.

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